舒尼替尼靶向治疗裸鼠膀胱癌移植瘤的效果

TARGETED TREATMENT OF SUNITINIB MALATE FOR TRANSPLATATION BLADDER CANCER IN ATHYMIC MICE

目的观察舒尼替尼对裸鼠膀胱癌移植瘤的靶向治疗作用。方法建立裸鼠皮下人膀胱癌移植瘤模型,随机分为实验组和对照组(各6只),实验组裸鼠用舒尼替尼40 mg/kg灌胃,每天1次;对照组给予等体积蒸馏水灌胃。观察肿瘤的生长情况;用免疫组化法检测肿瘤CD34、Ki67的表达,计算肿瘤的微血管密度和增殖指数;用TUNEL法测肿瘤的凋亡指数。结果实验组裸鼠的肿瘤生长被明显抑制,抑瘤率为72.03%,肿瘤退缩率为43.42%。实验组微血管密度、肿瘤增殖指数明显低于对照组,凋亡指数高于对照组,差异均有显著性(t=10.222～18.700,P<0.05)。结论舒尼替尼可阻断裸鼠膀胱癌移植瘤血管的生成进程,使肿瘤体积退缩,对移植瘤起到了抑制作用。

Objective To evaluate the effect of targeted therapy with sunitinib malate on transplantation bladder cancer in athymic mice. Methods Models of human bladder cancer transplanted subcutaneously in 12 athymic mice were created,which were equally divided into experiment and control group in random.Intragastric administration of sunitinib malate（40 mg/kg daily） was given to mice in the experiment group,to those in the control group,an equal volume of distilled water was offered.The growth of tumor was observed;Immunohistochmistry was employed to detect the index of cell proliferation and the expressions of CD34 and Ki67,and calculate the microvessel density（MVD）;and TUNEL technique was used to detect apoptotic index. Results In the experiment group,the tumor growth was suppressed obviously with 72.03% of oncostatic rate,and 43.42% tumor-regression rate;the MVD and the index of cell proliferation were both significantly lower than that of the control group（t=18.700,10.222;P0.05）,while the cell apoptotic index was higher than that of the control group（t=17.343,P0.05）. Conclusion Sunitinib malate can block the angiogenesis of transplanted bladder cancer in athymic mice,shrink the volume of tumor,thus inhibiting transplantation tumor.